Sedatives May Raise Risk of Pneumonia

Taking benzodiazepines may raise the risk of pneumonia as well as the likelihood of dying from the disease, researchers found.

Action Points

Note that in this case-control study of community-acquired pneumonia, exposure to benzodiazepines was associated with an increased risk of pneumonia.

Note also that benzodiazepines were associated with increased 30-day and long-term mortality in patients with a prior diagnosis of community-acquired pneumonia.

Taking benzodiazepines may raise the risk of pneumonia as well as the likelihood of dying from the disease, researchers found.

As a class, the sedatives were associated with more than a 50% increased chance of developing pneumonia (OR 1.54, 95% CI 1.42 to 1.67, P<0.001), Robert Sanders, PhD, of the Institute of Cognitive Neuroscience at University College London, and colleagues reported online in Thorax.

They also were tied to a 22% higher risk of 30-day and a 32% higher risk of long-term mortality, the researchers reported.

"Further research is required into the immune safety profile of benzodiazepines," they wrote.

Animal studies have shown that some benzodiazepines increase susceptibility to infection, and the class has been associated with infections and sepsis mortality in critically ill patients.

To further understand the relationship, Sanders and colleagues conducted a nested case-control study involving 4,964 cases of community-acquired pneumonia and 29,697 controls from the Health Improvement Network, a database of primary care patients in the U.K.

They found that all benzodiazepines, with the exception of chlordiazepoxide (Librium), were individually associated with an increased risk of the disease (P<0.001 for all):

Diazepam (OR 1.49, 95% CI 1.34 to 1.65)

Lorazepam (OR 2.20, 95% CI 1.68 to 2.89)

Temazepam (OR 1.87, 95% CI 1.70 to 2.06)

Chlordiazepoxide on its own likely didn't affect risk of infection because it's used to treat alcohol dependence and its effects were probably "dwarfed by the underlying disease," the researchers wrote.

They also found that zopiclone (Lunesta), which isn't a benzodiazepine but acts on GABA receptors, came with a significantly higher risk of developing pneumonia (OR 1.98, 95% CI 1.49 to 2.81, P<0.001).

With regard to mortality, benzodiazepines as a class were associated with a significantly higher risk of both 30-day and long-term death (HR 1.22, 95% CI 1.06 to 1.39 and HR 1.32, 95% CI 1.19 to 1.47, respectively).

All four benzodiazepines individually affected long-term mortality, the researchers reported, but only diazepam and lorazepam affected 30-day mortality on their own.

Sanders and colleagues noted that the study was limited because it couldn't exclude the possibility of unmeasured confounders, and also by the fact that prescription data were used as a proxy for exposure to the drugs.

Its design also poses the possibility of selection bias and precludes the ability to establish causality.

They concluded that future prospective cohort studies are needed to further investigate the relationship between benzodiazepines and infection, adding that other drugs targeting GABA receptors, such as topiramate, should be investigated as well.

The study was supported by the Medical Research Council and the GSK/British Lung Foundation.

The researchers reported no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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